Guidelines for the diagnosis, evaluation and management of chronic hypoparathyroidism

Publication: 23/09/2020  
Next review: 23/09/2023  
Clinical Guideline
ID: 6749 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2020  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidelines for the diagnosis, evaluation and management of chronic hypoparathyroidism

Summary of Guideline

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This guideline should be used by any medical professionals in Leeds to guide initial diagnosis and referral of patients with suspected chronic hypoparathyroidism. The guidelines should thereafter act as a standardising method to allow optimal treatment and monitoring of these patients. There may be additional use in aiding the identification of patients failing to meet treatment targets on conventional treatment and thus meeting criteria for consideration of Natpar treatment.

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Diagnosis and investigation

 In order to satisfy a diagnosis of hypoparathyroidism the following criteria must be met:

  • Hypocalcaemia: albumin-adjusted serum calcium below normal range (<2.20 mmol) on at least 2 occasions separated by at least 2 weeks.
  • Undetectable or inappropriately low PTH: in the presence of hypocalcaemia on at least two occasions.
  • Phosphate levels in upper normal or elevated range (not essential)
  • Considered chronic hypoparathyroidism if criteria met after 6 months.

Following biochemical diagnosis of chronic hypoparathyroidism, patients should be referred to the specialist Calcium Clinic via standard referral processes to endocrinology at Leeds Teaching Hospitals NHS Trust. The referral will be triaged to the appropriate clinic by Consultant Endocrinologists. A full evaluation to establish possible aetiology will take place. Aspects covered should at least include:

  1. Symptom assessment: symptoms of hypocalcaemia, gastrointestinal symptoms, renal symptoms, fracture history, consider quality of life including mood assessment
  2. Past medical history: previous neck surgery, radiation, infiltrative disorders, autoimmune disorders, HIV, haemochromatosis, malignancy
  3. Physical assessment: ophthalmology assessment for cataracts and calcifications, anterior neck for evidence of previous surgery, neuromuscular irritability (Trousseau’s sign, Chvostek’s), mucosal candidiasis, skin for vitiligo, range of motion of joints.
  4. Family history: Any family history of hypoparathyroidism, other endocrine deficiencies, specific autoimmune conditions
  5. Baseline imaging of target organs: imaging for basal ganglia/ other intracerebral calcifications, abdominal ultrasound for renal stones or calcifications.
  6. Full biochemical assessment in addition to calcium and PTH to confirm the diagnosis: phosphate, magnesium, 25-hydroxyvitamin D, U&E’s (specifically creatinine), parathyroid antibodies.
  7. Urine biochemical evaluation: 24-hour urine for calcium excretion
  8. Consider genetics: particularly if young, family history or multiple autoimmune characteristics. Consider screening for mutations in genes: PTH, CASR, GCM2 and GNA11 for isolated Hypoparathyroidism and for hypoparathyroidism associated syndromes; AIRE (autoimmune polyglandular syndrome type 1), chromosome 22q (DiGeorge syndrome), TBCE (Kenny-Caffey Type 1), FAM111A (Kenny-Caffey type 2), mitochondrial DNA.

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The focus of routine management of patients with confirmed chronic hypoparathyroidism should include:

  1. Prevention of the signs and symptoms associated with hypocalcaemia (including tetany, perioral paraesthesia, hand/feet numbness and tingling, ‘brain fog’, prolonged QTc on ECG).
  2. Maintain serum adjusted calcium slightly below/low-normal of reference range i.e. 2.10-2.30 mmol/l.
  3. Maintain a calcium-phosphate product of <4.4 mmol2/l2
  4. Avoid hypercalciuria (>7.5mmol/24hours)
  5. Avoidance of hypercalcaemia
  6. Avoid renal and other extra-skeletal calcifications

Typical treatments and dosing are listed below:

  • Oral calcium- typically calcium carbonate is preferred as has higher percentages of elementary calcium (40% vs 20% in calcium citrate). The amount of calcium supplementation required is patient specific but can be as high as 9g/d.
  • Active vitamin D (usually alfacalcidol or calcitriol). Dosing is patient specific and requires 1-2 weekly biochemical monitoring until a stable regime is determined. Typical dosing for calcitriol is 0.25-0.5 micrograms once-twice daily. Typical dosing for alfacalcidol is 0.5-4 micrograms once daily.
  • Thiazide diuretics can be considered in the presence of persistent hypercalciuria and can be accompanied by a low salt diet.

Following commencement of treatment as listed above, there must be consideration for long-term management of patients with chronic hypoparathyroidism both in terms of complication of the disease itself and potential consequences of treatment. Suggested monitoring includes:

  • Biochemistry: Following stabilisation of biochemistry on treatment, monitoring of calcium, phosphate, magnesium, 25 hydroxyvitamin D, U&Es along with PTH should take place at regular time intervals, every 3-6 months.
  • Urine calcium: monitoring of 24-hour urine calcium should take place annually.
  • Renal imaging: Repeat renal imaging (usually renal ultrasound) for evidence of renal calculi or nephrocalcinosis should take place 2 yearly minimum or sooner if development of symptoms or elevation of serum creatinine.
  • Ophthalmic assessment: To ensure there has not been development of calcification or cataracts, this should take place yearly and can be in the form of an annual optician review.  

NB: there is no evidence to suggest need for monitoring of bone mineral density by DXA scan, unless other risk factors for fracture.

PTH Replacement Therapy
In recent years there have been advances in the treatment of patients with chronic hypoparathyroidism, who, despite best efforts with the above treatment regimes have not achieved stability of disease in particular in terms of serum calcium, phosphate and urinary calcium excretion as well as quality of life measures.
Recombinant human PTH (rhPTH), Natpar, delivered as a daily SC injection, has been shown to achieve normocalcemia in several studies and was approved by the American Food and Drug Administration (FDA) in 2015, though strictly reserved for patients unable to meet management criteria targets, as listed above, on conventional therapy. The European medicines agency later followed suit.
Key studies demonstrating the efficacy and safety of Natpar in these patients include the REPLACE study and the RACE study with demonstration of normocalcemia, reduced calcium excretion and reduced serum phosphate with rhPTH during the timeframe of the studies. At present this must be applied for on a patient by patient basis based on not meeting management criteria, listed above, on conventional treatment.


  • Monitoring of Natpar is specific to individual patients. The management and monitoring plan will be determined by a specialist endocrinologist in the Calcium Clinic.

Criteria for Natpar use:

  • Failure of conventional therapy to adequately control biochemistry, symptoms or undesirable clinical outcomes despite optimisation for more than 12 months by a Consultant Endocrinologist with expertise in the treatment of hypoparathyroidism via Calcium Clinic.


Record: 6749

To provide objective measures for the diagnosis of patients with potential chronic hypoparathyroidism and improve referral for specialist management and monitoring of these patients in line with international guidelines.

Clinical condition:

Chronic Hypoparathyroidism

Target patient group: Patients with possible or confirmed chronic hypoparathyroidism
Target professional group(s): Pharmacists
Secondary Care Doctors
Adapted from:

Evidence base

  1. Bollerslev, J., Rejnmark, L., Marcocci, C., Shoback, D., Sitges-Serra, A., van Biesen, W., & Dekkers, O. European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults. European Journal of Endocrinology, 173(2), G1-G20. 2015.
  2. Maria Luisa Brandi, John P. Bilezikian, Dolores Shoback, Roger Bouillon, Bart L. Clarke, Rajesh V. Thakker, Aliya A. Khan, John T. Potts, Jr, Management of Hypoparathyroidism: Summary Statement and Guidelines. The Journal of Clinical Endocrinology & Metabolism. 2016. 101(6):2273–2283.
  3. Vokes TJ, Mannstadt M, Levine MA, Clarke BL, Lakatos P, Chen K, Piccolo R, Krasner A, Shoback DM, Bilezikian JP. Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism. J Clin Endocrinol Metab. 2018. 103(2):722-731.
  4. Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, Lakatos P, Bajnok L, Garceau R, Mosekilde L, Lagast H, Shoback D, Bilezikian JP. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013. 1(4):275-83.

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

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